Safety and effectiveness of additional triamcinolone acetonide with endoscopic radial incision and cutting for benign stenosis of the lower gastrointestinal tract: A pilot study.

Objectives: Radial incision and cutting (RIC) is being investigated as an alternative endoscopic dilation method for lower intestinal tract stenosis, providing a high technical success rate and improving subjective symptoms. However, several patients develop re-stenosis following RIC. In this pilot study, we aimed to evaluate the safety and efficacy of triamcinolone acetonide (TA) addition after RIC. Methods: RIC with TA was performed in 20 patients with lower gastrointestinal tract stenosis. We evaluated the rate of adverse events 2 months after RIC with TA. We investigated the short- and long-term prognoses, as well as the improvement in subjective symptoms, using a visual analog scale. Results: The delayed bleeding rate after RIC was 23.8%. Endoscopic hemostasis was achieved in all patients with delayed bleeding. No perforations were observed. The cumulative re-stenosis-free, re-intervention-free, and surgery-free rates 1 year after RIC were 52.9%, 63.7%, and 85.2%, respectively. Subjective symptoms, including abdominal pain, abdominal bloating, nausea, and dyschezia, significantly improved after RIC with TA. Conclusion: Although additional TA administration after RIC could be safe, additional TA may not be effective on luminal patency after dilation. Further investigation is warranted.

Effectiveness of pelvic circumferential compression device for lower body trauma: Insights from a Japan Trauma Data Bank retrospective study.

Aim: Pelvic ring fractures (PRFs) due to high-energy trauma often result in severe bleeding and high mortality. Pelvic circumferential compression devices (PCCD) are widely used to stabilize PRF and decrease bleeding. However, evidence supporting their effectiveness is still inconclusive. Methods: We conducted an observational study using the Japan Trauma Data Bank (JTDB) from 2019 to 2021. Patients with blunt lower body trauma aged 15 years or older were included. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to evaluate the association of PCCD and mortality. Results: Of the 74,393 patients in the database, 235 PCCD group and 23,429 control group were analyzed. After PSM, 231 patients in both groups were enrolled. Crude analysis indicated significantly higher in-hospital mortality in the PCCD group (odds ratio (OR) = 3.8 [95% CI = 2.51-5.75]). However, PSM and IPTW analysis indicated that PCCD was associated with decreased in-hospital mortality (PSM: OR = 0.79 [0.43-1.42]; IPTW: OR = 0.73 [0.62-0.86]). In a subgroup analysis of the IPTW analysis, PCCD fitting resulted in increased in-hospital mortality in the group without PRF (OR = 2.08 [1.91-2.27]), a decrease in stable PRF (OR = 0.74 [0.6-0.91]), and a further decrease in unstable PRF (OR = 0.18 [0.12-0.27]). Additional factors, such as a fall from a height, a fall downstairs, and pre-hospital PCCD placement also influenced the treatment effect. Conclusion: The present, large, registry-based study found that PCCD reduced mortality in patients with a lower body injury, especially those with an unstable PRF.

A Phase II Clinical Trial to Study the Safety of Triamcinolone after Endoscopic Radial Incision and Cutting Dilatation for Benign Stenosis of the Lower Gastrointestinal Tract: A Study Protocol.

BACKGROUND: Lower gastrointestinal tract stenosis is commonly diagnosed and is typically treated with surgery or endoscopic balloon dilation (EBD). Radial incision and cutting (RIC) is a novel treatment approach that has several benefits compared with EBD and surgery. Although RIC has demonstrated a high technical success rate and has been shown to improve subjective symptoms, previous studies revealed that restenosis after RIC remain unsolved. Herein, we report the design of a prospective, multicenter, single-arm, interventional, phase II trial to evaluate the safety of local triamcinolone acetonide (TA) administration and its feasibility in preventing restenosis after RIC for lower gastrointestinal tract stenosis. METHODS: The major inclusion criteria are age 20-80 years and the presence of benign stenosis in the lower gastrointestinal tract accessible by colonoscope. We will perform RIC followed by local administration of TA to 20 participants. The primary outcome is the safety of local TA administration, which will be assessed by determining the frequency of adverse events of special interest. The secondary outcomes are the technical success rate of RIC, duration of procedure, improvement in subjective symptoms, and duration of hospitalization. The outcomes, improvement in subjective symptoms, and long-term results will be evaluated using descriptive statistics, Student's t-test, and Kaplan-Meier curve, respectively. DISCUSSION: This explorative study will provide useful information regarding the safety of TA administration after RIC, which may contribute to further investigations.

Underuse of heart failure medications and poor long-term prognosis in chronic heart failure patients with polypharmacy - A report from the CHART-2 study.

Background: In patients with chronic heart failure (CHF), comorbidities are often managed with multiple medications, characterized by polypharmacy, leading to increased risk of potentially inappropriate medication and adverse effects. Methods: We studied 4,876 consecutive patients with CHF (Stage C/D, age 69.0 ± 12.3 years) in the CHART-2 study to evaluate the association among polypharmacy, underuse of HF medications, and all-cause death. Polypharmacy was defined as the daily use of ≥ 8 medications for the survival classification and regression tree analysis. Results: The average number of medications was 10 in the polypharmacy group and 5 in the non-polypharmacy group, respectively. Over a median of 8.3 (4.1-11.7) years, the incidence rate of all-cause death was significantly higher in the polypharmacy group (n = 2,108) than in the non-polypharmacy group (57.3 % vs. 40.6 %; adjusted hazard ratio [aHR] 1.34 (95 %CI, 1.22-1.48), P < 0.001), even in age < 55 years (26.6 % vs. 14.3 %; adjusted hazard ratio [aHR] 1.61 (95 %CI, 1.04-2.50), P = 0.033). In patients with polypharmacy, those without renin-angiotensin system inhibitors (RAS-I) and/or beta-blockers (N = 1,023) were associated with increased incidence of all-cause death as compared with those with both medications (aHR 1.18; 95 %CI 1.04-1.35, P = 0.012). Conclusions: Polypharmacy was associated with poor long-term prognosis, even in younger patients with CHF. Among 4,876 patients with CHF, 1023 (20.9%) with polypharmacy and underuse of RAS-I and/or beta-blocker were associated with increased risk of all-cause death.

Clinical and Sociodemographic Factors Associated With Health-Related Quality of Life in Patients With Adult Congenital Heart Disease　- A Nationwide Cross-Sectional Multicenter Study.

BACKGROUND: Little is known about clinical or sociodemographic factors that influence health-related quality of life (HRQoL) in patients with adult congenital heart disease (ACHD).Methods and Results: We conducted a nationwide prospective cross-sectional multicenter study at 4 large ACHD centers in Japan. From November 2016 to June 2018, we enrolled 1,223 ACHD patients; 1,025 patients had an HRQoL score. Patients completed a questionnaire survey, including sociodemographic characteristics, and the 36-Item Short-Form Health Survey (SF-36). To determine factors associated with HRQoL, correlations between 2 SF-36 summary scores (i.e., physical component score [PCS] and mental component score [MCS]) and other clinical or sociodemographic variables were examined using linear regression analysis. In multivariable analysis, poorer PCS was significantly associated with 11 variables, including older age, higher New York Heart Association class, previous cerebral infarction, being unemployed, and limited participation in physical education classes and sports clubs. Poorer MCS was associated with congenital heart disease of great complexity, being part of a non-sports club, current smoking, and social drinking. Student status and a higher number of family members were positively correlated with MCS. CONCLUSIONS: This study demonstrates that HRQoL in ACHD patients is associated with various clinical and sociodemographic factors. Further studies are needed to clarify whether some of these factors could be targets for future intervention programs to improve HRQoL outcomes.

Natural history of Behçet's disease focusing on remission of oral ulcers.

OBJECTIVES: To describe the long-term clinical course of each manifestation of Behçet's disease (BD) and clarify factors involved in oral ulcer (OU) remission using clinical information of BD patients. METHODS: We retrospectively studied 155 BD patients visiting our hospital (1989-2020). We defined remission criteria for each manifestation and examined long-term clinical changes. Classification and regression trees and multivariable analyses were performed to investigate OU prognostic factors; hazard ratios were used to assign scores to prognostic factors deemed significant [OU prognosis score (OuP score)]. Risk stratification was examined by dividing the OuP scores into four stages. RESULTS: OUs appeared earliest, with the slowest decline in prevalence observed post-BD diagnosis. OU presence was the most common factor inhibiting complete remission. Young age at OU onset, never smoker, presence of genital ulcers, positive pathergy test, no usage of tumour necrosis factor inhibitors or of immunosuppressants, and long-term non-treatment or symptomatic treatment for OUs were poor OU prognostic factors. Based on multivariable analysis, the area under the curve of the OuP score to predict OU prognosis was 0.678. CONCLUSIONS: Remission criteria for each symptom clarified that OU had the greatest impact on complete BD remission. Faster OU remission was associated with earlier OU therapeutic intervention other than symptomatic treatment.

Usefulness of cardiac magnetic resonance for early detection of cancer therapeutics-related cardiac dysfunction in breast cancer patients.

BACKGROUND: Prognosis of breast cancer patients has been improved along with the progress in cancer therapies. However, cancer therapeutics-related cardiac dysfunction (CTRCD) has been an emerging issue. For early detection of CTRCD, we examined whether native T1 mapping and global longitudinal strain (GLS) using cardiac magnetic resonance (CMR) and biomarkers analysis are useful. METHODS: We prospectively enrolled 83 consecutive chemotherapy-naïve female patients with breast cancer (mean age, 56 ± 13 yrs.) between 2017 and 2020. CTRCD was defined based on echocardiography as left ventricular ejection fraction (LVEF) below 53% at any follow-up period with LVEF>10% points decrease from baseline after chemotherapy. To evaluate cardiac function, CMR (at baseline and 6 months), 12­lead ECG, echocardiography, and biomarkers (at baseline and every 3 months) were evaluated. RESULTS: A total of 164 CMRs were performed in 83 patients. LVEF and GLS were significantly decreased after chemotherapy (LVEF, from 71.2 ± 4.4 to 67.6 ± 5.8%; GLS, from -27.9 ± 3.9 to -24.7 ± 3.5%, respectively, both P < 0.01). Native T1 value also significantly elevated after chemotherapy (from 1283 ± 36 to 1308 ± 39 msec, P < 0.01). Among the 83 patients, 7 (8.4%) developed CTRCD. Of note, native T1 value before chemotherapy was significantly higher in patients with CTRCD than in those without it (1352 ± 29 vs. 1278 ± 30 msec, P < 0.01). The multivariable logistic regression analysis revealed that native T1 value was an independent predictive factor for the development of CTRCD [OR 2.33; 95%CI 1.15-4.75, P = 0.02]. CONCLUSIONS: These results indicate that CMR is useful to detect chemotherapy-related myocardial damage and predict for the development of CTRCD in breast cancer patients.

The concerted elevation of conjugation reactions is associated with the aggravation of acetaminophen toxicity in Akr1a-knockout mice with an ascorbate insufficiency.

AIMS: Acetaminophen (APAP) is a relatively safe analgesic drug, but overdosing can cause acute liver failure. Ingested APAP is detoxified by metabolic conversion through conjugation reactions with glucuronate, sulfate, or glutathione (GSH). The consumption of GSH through conjugation as well as mitochondrial dysfunction is considered to be responsible for the increased susceptibility to APAP-induced hepatotoxicity. Compared to wild-type (WT) mice, Akr1a-knockout (KO) mice are vulnerable to developing hepatotoxicity due to the fact that ascorbate synthesis is attenuated. We used such KO mice to investigate how these conjugation reactions are involved in the hepatotoxicity caused by an overdose of APAP under ascorbate-deficient conditions. MAIN METHODS: APAP (400 mg/kg) was intraperitoneally administered to WT mice and KO mice. In addition to histological and blood biochemical analyses, metabolites in the liver, blood plasma, and urine were measured at several time points by liquid chromatography-mass spectrometry. KEY FINDINGS: Liver damage occurred earlier in the KO mice than in the WT mice. The levels of APAP-Cys, a final metabolite of GSH-conjugated APAP, as well as glucuronidated APAP and sulfated APAP were all higher in the KO mice compared to the WT mice. Treatment of the APAP-administered KO mice with N-acetylcysteine or supplementation of ascorbate suppressed the conjugation reactions at 6 h after APAP had been administrated, which mitigated the degree of liver damage. SIGNIFICANCE: An ascorbate deficiency coordinately stimulates conjugation reactions of APAP, which, combined with the mitochondrial damage caused by APAP metabolites, collectively results in the aggravation of the acute liver failure.

Impact of statins in patients with vasospastic angina: A multicenter registry study of the Japanese Coronary Spasm Association.

BACKGROUND: Statins are generally used for patients with coronary artery disease. However, the impact of statins in patients with vasospastic angina (VSA) is not fully understood. METHODS: In a multicenter registry study of the Japanese Coronary Spasm Association (n = 1429), patients with or without statins were compared. The primary endpoint was major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, unstable angina, heart failure, and appropriate implantable cardioverter defibrillator shock. Propensity score matching and a multivariable Cox proportional hazard model were used to adjust for selection bias in treatment and potential confounding factors. RESULTS: In the whole population, 469 patients received statins, while 960 patients did not receive statins. Patients with statins had a greater prevalence of comorbidities, including hypertension, diabetes, dyslipidemia, and smoking, in comparison to those without statins. The prevalence rates of previous myocardial infarction, significant organic stenosis, and medication use (including calcium channel blockers, angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, and beta blockers) were greater in patients with statins than in those without statins. After propensity matching (n = 211 for both groups), a Kaplan-Meier curve analysis revealed that the incidence of MACE was comparable between patients with and without statins (p = 0.686). MACEs occurred in 6.0% of patients with statins and in 5.9% of those without statins (p = 0.98). CONCLUSION: In this multicenter registry study, statin therapy did not reduce clinical events in VSA patients.

Prognostic impact of a history of cancer and atrial fibrillation in antithrombotic therapy for chronic heart failure.

AIMS: This study aimed to examine the prognostic significance of a history of cancer and atrial fibrillation (AF) in antithrombotic therapy for patients with chronic heart failure (CHF). METHODS AND RESULTS: We enrolled consecutive 4876 CHF patients (69 ± 12 years; women, 31.9%) in our multicentre, hospital-based cohort study, the Chronic Heart Failure Analysis and Registry in the Tohoku District-2 (CHART-2), with a median follow-up of 8.7 years. Among them, 14% and 41% had a history of cancer and AF, respectively. AF patients with a history of cancer were older, more frequently men. History of cancer was not statistically associated with higher rate of composite of stroke, systemic thrombosis, and major bleeding defined by International Society on Thrombosis and Haemostasis [Fine-Gray sub-distribution hazard ratio (sHR) accounting for the competing risk of all-cause death, 0.91; 95% confidence interval (CI), 0.56-1.48; P = 0.715]. The patients with history of cancer and AF had a heightened risk for the composite of stroke, systemic thrombosis, and major bleeding (sHR, 1.64; 95% CI, 1.04-2.60; P = 0.033), especially in those aged >75 years (sHR, 2.14; 95% CI, 1.01-4.53; P = 0.046) and those with ischaemic heart disease (IHD; 2.48; 1.30-4.72; P = 0.006). Furthermore, 36% of AF patients with a history of cancer did not receive anticoagulant therapy. CONCLUSIONS: The CHF patients with history of cancer and AF had higher risk for stroke, systemic thrombosis, and major bleeding, especially in the elderly and those with IHD, but considerable number of the patients did not receive anticoagulant therapy, indicating the need for better optimal anticoagulation strategy.

Association between IDH mutational status and tumor-associated epilepsy or venous thromboembolism in patients with grade II and III astrocytoma.

In previous studies, isocitrate dehydrogenase (IDH) mutations were associated with tumor-associated epilepsy (TAE) and venous thromboembolism (VTE). We examined the relationship between IDH mutations in grade II/III astrocytomas and TAE/VTE according to the 2016 World Health Organization classification. The clinical data of patients with newly diagnosed grade II/III gliomas who were treated at Tohoku University Hospital from January 2010 to December 2018 were reviewed. Associations between TAE or VTE and the clinical/biological characteristics, histology, and IDH1/2 mutational status in patients with grade II/III gliomas were evaluated. Of the initial 137 patients (290 hospitalizations), 117 patients (203 hospitalizations) were included in the TAE group and 124 patients (213 hospitalizations) were included in the VTE group. Seventy-eight patients (66.7%) in the TAE group were diagnosed with astrocytoma and 38/78 (48.3%) presented with TAE. According to the multivariable analysis, the IDH mutational status and male sex were associated independently with an increased risk of TAE (p < 0.05). Eighty-five patients (68.5%) in the VTE group were diagnosed with astrocytoma. VTE was observed in 16/161 (9.9%) hospitalizations. According to the multivariable analysis, age, diffuse astrocytoma histology, and resection were associated independently with an increased risk of VTE. The decision tree analysis showed that TAE was more frequent in younger patients while VTE was more frequent in older patients. This study demonstrated that the IDH mutational status was associated with TAE but not with VTE. Therefore, a future large-scale study is needed to provide sufficient evidence. TAE was more common in young patients, while VTE was more common in the elderly.

Pleiotropic Actions of Aldehyde Reductase (AKR1A).

We provide an overview of the physiological roles of aldehyde reductase (AKR1A) and also discuss the functions of aldose reductase (AKR1B) and other family members when necessary. Many types of aldehyde compounds are cytotoxic and some are even carcinogenic. Such toxic aldehydes are detoxified via the action of AKR in an NADPH-dependent manner and the resulting products may exert anti-diabetic and anti-tumorigenic activity. AKR1A is capable of reducing 3-deoxyglucosone and methylglyoxal, which are reactive intermediates that are involved in glycation, a non-enzymatic glycosylation reaction. Accordingly, AKR1A is thought to suppress the formation of advanced glycation end products (AGEs) and prevent diabetic complications. AKR1A and, in part, AKR1B are responsible for the conversion of d-glucuronate to l-gulonate which constitutes a process for ascorbate (vitamin C) synthesis in competent animals. AKR1A is also involved in the reduction of S-nitrosylated glutathione and coenzyme A and thereby suppresses the protein S-nitrosylation that occurs under conditions in which the production of nitric oxide is stimulated. As the physiological functions of AKR1A are currently not completely understood, the genetic modification of Akr1a could reveal the latent functions of AKR1A and differentiate it from other family members.

Prognostic model for patients with advanced cancer using a combination of routine blood test values.

PURPOSE: The purpose of this study was to develop a simple prognostic model based on objective indicators alone, i.e., routine blood test data, without using any subjective variables such as patient's symptoms and physician's prediction. METHODS: The subjects of this retrospective study were patients at the palliative care unit of Tohoku University Hospital, Japan. Eligible patients were over 20 years old and had advanced cancer (n = 225). The model for predicting survival was developed based on Cox proportional hazards regression models for univariable and multivariable analyses of 20 items selected from routine blood test data. All the analyses were performed according to the TRIPOD statement ( https://www.tripod-statement.org/ ). RESULTS: The univariable and multivariable regression analyses identified total bilirubin, creatinine, urea/creatinine ratio, aspartate aminotransferase, albumin, total leukocyte count, differential lymphocyte count, and platelet/lymphocyte ratio as significant risk factors for mortality. Based on the hazard ratios, the area under the curve for the new risk model was 0.87 for accuracy, 0.83 for sensitivity, and 0.74 for specificity. Diagnostic accuracy was higher than provided by the Palliative Prognostic Score and the Palliative Prognostic Index. The Kaplan-Meier analysis demonstrated a survival significance of classifying patients according to their score into low-, medium-, and high-mortality risk groups having median survival times of 67 days, 34 days, and 11 days, respectively (p < 0.001). CONCLUSIONS: We developed a simple and accurate prognostic model for predicting the survival of patients with advanced cancer based on routine blood test values alone that may be useful for appropriate advanced care planning in a palliative care setting.

Prognostic significance of propofol-based intravenous anesthesia in early-stage lung cancer surgery.

PURPOSE: The purpose of this study was to assess whether the anesthetic type is associated with the prognosis of pathological stage I non-small cell lung cancer (NSCLC). METHODS: Clinicopathological data from 431 consecutive patients who underwent lobectomy for NSCLC between 2010 and 2016 were collected. Patients were classified into groups according to the type of anesthesia: propofol-based total intravenous anesthesia (TIVA) or inhalation anesthesia (INHA). We investigated the prognostic differences between these two groups. RESULTS: A total of 72 patients in the TIVA group and 158 patients in the INHA group were eligible for the analysis. Recurrence was observed in 4 (5.6%) patients in the TIVA group and 19 (12.0%) patients in the INHA group (P = 0.159), and all-cause death occurred in 4 (5.6%) patients in the TIVA group and 24 (15.2%) patients in the INHA group (P = 0.049). The 5-year recurrence-free survival (RFS) and overall survival rates of the TIVA/INHA groups were 91.7%/77.4% and 94.4%/83.5%, respectively. TIVA was associated with a significantly better prognosis. A multivariable analysis of factors associated with RFS revealed that the type of anesthesia as a significant prognostic factor (P = 0.047). CONCLUSION: Propofol-based TIVA was associated with a better prognosis in comparison to INHA in patients with surgically resected pathological stage I NSCLC.

Low-intensity pulsed ultrasound ameliorates cardiac diastolic dysfunction in mice: a possible novel therapy for heart failure with preserved left ventricular ejection fraction.

AIMS: Heart failure with preserved left ventricular ejection fraction (HFpEF) is a serious health problem worldwide, as no effective therapy is yet available. We have previously demonstrated that our low-intensity pulsed ultrasound (LIPUS) therapy is effective and safe for angina and dementia. In this study, we aimed to examine whether the LIPUS therapy also ameliorates cardiac diastolic dysfunction in mice. METHODS AND RESULTS: Twelve-week-old obese diabetic mice (db/db) and their control littermates (db/+) were treated with either the LIPUS therapy [1.875 MHz, 32 cycles, Ispta (spatial peak temporal average intensity) 117-162 mW/cm2, 0.25 W/cm2] or placebo procedure two times a week for 4 weeks. At 20-week-old, transthoracic echocardiography and invasive haemodynamic analysis showed that cardiac diastolic function parameters, such as e', E/e', end-diastolic pressure-volume relationship, Tau, and dP/dt min, were all deteriorated in placebo-treated db/db mice compared with db/+ mice, while systolic function was preserved. Importantly, these cardiac diastolic function parameters were significantly ameliorated in the LIPUS-treated db/db mice. We also measured the force (F) and intracellular Ca2+ ([Ca2+]i) in trabeculae dissected from ventricles. We found that relaxation time and [Ca2+]i decay (Tau) were prolonged during electrically stimulated twitch contractions in db/db mice, both of which were significantly ameliorated in the LIPUS-treated db/db mice, indicating that the LIPUS therapy also improves relaxation properties at tissue level. Functionally, exercise capacity was also improved in the LIPUS-treated db/db mice. Histologically, db/db mice displayed progressed cardiomyocyte hypertrophy and myocardial interstitial fibrosis, while those changes were significantly suppressed in the LIPUS-treated db/db mice. Mechanistically, western blot showed that the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cGMP-protein kinase G (PKG) pathway and Ca2+-handling molecules were up-regulated in the LIPUS-treated heart. CONCLUSIONS: These results indicate that the LIPUS therapy ameliorates cardiac diastolic dysfunction in db/db mice through improvement of eNOS-NO-cGMP-PKG pathway and cardiomyocyte Ca2+-handling system, suggesting its potential usefulness for the treatment of HFpEF patients.

Beneficial effects of exercise training on physical performance in patients with vasospastic angina.

AIMS: In vasospastic angina (VSA), coronary vasomotion abnormalities could develop not only in epicardial coronary arteries but also in coronary microvessels, where calcium channel blockers (CCBs) have limited efficacy. However, efficacy of exercise training for VSA remains to be elucidated. We thus aimed to examine whether vasodilator capacity of coronary microvessels is impaired in VSA patients, and if so, whether exercise exerts beneficial effects on the top of CCBs. METHODS: We performed 2 clinical protocols. In the protocol 1, we measured myocardial blood flow (MBF) using adenosine-stress dynamic computed tomography perfusion (CTP) in 38 consecutive VSA patients and 17 non-VSA controls. In the protocol 2, we conducted randomized controlled trial, where 20 VSA patients were randomly assigned to either 3-month exercise training group (Exercise group) or Non-Exercise group (n= 10 each). RESULTS: In the protocol 1, MBF on CTP was significantly decreased in the VSA group compared with the Non-VSA group (138 ± 6 vs 166 ± 10 ml/100 g/min, P = 0.02). In the protocol 2, exercise capacity was significantly increased in the Exercise group than in the Non-Exercise group (11.5 ± 0.5 to 15.4 ± 1.8 vs 12.6 ± 0.7 to 14.0 ± 0.8 ml/min/kg, P < 0.01). MBF was also significantly improved after 3 months only in the Exercise group (Exercise group, 145 ± 12 to 172 ± 8 ml/100 g/min, P < 0.04; Non-Exercise group, 143 ± 14 to 167 ± 8 ml/100 g/min, P = 0.11), although there were no significant between-group differences. CONCLUSIONS: These results provide the first evidence that, in VSA patients, exercise training on the top of CCBs treatment may be useful to improve physical performance, although its effect on MBF may be minimal.

The impact of antiplatelet therapy on patients with vasospastic angina: A multicenter registry study of the Japanese Coronary Spasm Association.

BACKGROUND: Antiplatelet therapy (APT) is generally used in patients with coronary artery disease. However, for patients with vasospastic angina (VSA), the impact of APT is not fully understood. METHODS: In a multicenter registry study of the Japanese Coronary Spasm Association (n = 1429), patients with or without APT were compared. The primary endpoint was major adverse cardiac events (MACEs), defined as cardiac death, non-fatal myocardial infarction, unstable angina, heart failure and appropriate ICD (Implantable cardioverter defibrillator) shock. Propensity score matching and a multivariable cox proportional hazard model were used to adjust for selection bias for treatment and potential confounding factors. RESULTS: In the whole population, 669 patients received APT, while 760 patients did not receive APT. Patients with APT had a greater prevalence of comorbidities, such as hypertension, diabetes, dyslipidemia and smoking, than those without APT. The prevalences of previous myocardial infarction, spontaneous ST changes, significant organic stenosis and medications including calcium channel blocker, nitrate, statin and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were greater in patients with APT than those without APT. After propensity matching (n = 335 for both groups), during the median follow-up period of 32 months, the incidence rate of MACE was comparable between the patients with and without APT (P = 0.24). MACEs occurred in 5.7% of patients with APT and in 3.6% of those without APT (P = 0.20). All-cause death occurred in 0.6% of patients with APT and 1.8% of those without APT (p = 0.16). CONCLUSION: In this multicenter registry study, anti-platelet therapy exerted no beneficial effects for VSA patients.

Clinical characteristics and prognostic factors in elderly patients with chronic heart failure -A report from the CHART-2 study.

BACKGROUND: Since most of the randomized clinical trials for heart failure (HF) were designed to exclude elderly patients, limited data are available on their clinical characteristics, prognosis, and prognostic factors. METHODS: We compared clinical characteristics, prognosis, and prognostic factors among Stage C/D HF patients in our CHART-2 Study (N = 4876, mean 69 years, women 32%, 6.3-year follow-up) by age (G1, ≤64 years, N = 1521; G2, 65-74 years, N = 1510; and G3, ≥75 years, N = 1845). RESULTS: From G1 to G3, the prevalence of women, left ventricular ejection fraction (LVEF) and plasma levels of B-type natriuretic peptide (BNP) increased (all P < 0.001). Similarly, 5-year mortality increased (9.9, 17.3 to 39.9%, P < 0.001) along with a decrease in proportion of cardiovascular death and an increase in non-cardiovascular death in both sexes. While all-cause and cardiovascular mortality was comparable between the sexes, women had significantly lower incidence of non-cardiovascular death than men in G2 and G3, which was attributable to the higher incidence of cancer death and pneumonia death in men than in women. Although NYHA functional class III-IV, chronic kidney disease, cancer, LVEF, and BNP had significant impacts on all-cause death in all groups, their impacts were less evident in G3 as compared with G1. CONCLUSIONS: The elderly HF patients, as compared with younger HF patients, were characterized by more severe clinical background, increased proportion of non-cardiovascular death and worse prognosis with different impacts of prognostic factors across the age groups.

Increased risk of cancer death in patients with chronic heart failure with a special reference to inflammation-A report from the CHART-2 Study.

BACKGROUND: Although several factors, including heart failure (HF) and inflammation, are known to increase the incidence of cancer, it remains unknown whether HF may increase cancer mortality, especially with a reference to inflammation. METHODS AND RESULTS: We examined 8843 consecutive cardiovascular patients without a prior history of cancer in our CHART-2 Study (mean 68 yrs., female 30.9%). As compared with patients without HF (Stage A/B, N = 4622), those with HF (Stage C/D, N = 4221) were characterized by higher prevalence of diabetes, previous myocardial infarction, atrial fibrillation, and stroke. During the median 6.5-year follow-up (52,675 person-years), 282 cancer deaths occurred. HF patients had significantly higher cancer mortality than those without HF in both the overall (3.7 vs, 2.8%, hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.12-1.79, P = 0.004) and the propensity score-matched cohorts (HR 1.46, 95%CI 1.10-1.93, P = 0.008), which was confirmed in the competing risk models. The multivariable Cox proportional hazard model in the matched cohort showed that HF was associated with increased cancer mortality in patients with C-reactive protein (CRP) ≥ 2.0 mg/L (HR 1.87, 95%CI 1.18-2.96, P = 0.008) at baseline, but not in those with CRP < 2.0 mg/L (HR 0.89, 95%CI 0.54-1.45, P = 0.64) (P for interaction = 0.03). Furthermore, temporal changes in CRP levels were associated with cancer death in the overall cohort; HF patients with CRP ≥ 2.0 mg/L at both baseline and 1-year had significantly increased cancer death, while those with CRP ≥ 2.0 mg/L at baseline and < 2.0 mg/L at 1-year not. CONCLUSIONS: These results provide the first evidence that HF is associated with increased cancer death, especially when associated with prolonged inflammation.

Effects of Hepatitis C Virus Antibody-Positivity on Cardiac Function and Long-Term Prognosis in Patients With Adult Congenital Heart Disease.

It was reported that hepatitis C virus (HCV) antibody-positivity adversely affects cardiac function. As the screening for HCV began in 1992, we hypothesized that HCV antibody-positive rate would be high in adult congenital heart disease (ACHD) patients who underwent heart surgery before 1992 and adversely affected cardiac function and long-term prognosis. We retrospectively enrolled 243 ACHD patients (mean age 25.9 years) who underwent cardiac surgery before 1992 and visited our hospital from 1995 to 2015. We compared clinical characteristics including cardiac function and long-term prognosis between HCV antibody-positive (n = 48) and antibody-negative (n = 195) patients. The composite end point (CEP) included cardiac death, heart failure hospitalization, lethal ventricular arrhythmias, and cardiac reoperation. The prevalence of reduced systemic ventricular ejection fraction <50% was significantly higher in the HCV antibody-positive group compared with the HCV antibody-negative group (17 vs 5.4%, p = 0.014). During a mean follow-up period of 10.1 years (interquartile range 6 to 14 years), the CEP was noted in 51 patients. Kaplan-Meier analysis showed the HCV antibody-positive group had significantly poor event-free survival than the HCV antibody-negative group (log-rank, p = 0.002). In contrast, HCV ribonucleic acid-positivity was not a significant predictor of the CEP in the HCV antibody-positive group (log-rank, p = 0.442). Furthermore, the HCV antibody-positivity was significantly associated with the CEP in both univariable and multivariable Cox regression models (hazard ratio 2.37, 95% confident interval 1.32 to 4.15, p = 0.005 and 1.96, 1.06 to 3.63, p = 0.032, respectively). In conclusion, these results suggest that more attention should be paid to HCV antibody-positivity in the management of ACHD patients.